Little is known of the adhesive interactions between platelets, leukocytes, and endothelial cells, interactions that are involved in the processes of inflammation, atherogenesis, and thrombosis. The PI has identified specific interactions between the platelet gpIb-IX-V complex and members of the selectin and leukocyte integrin families. Each of these interactions is mediated by the gpIb-alpha. The hypothesis that drives this application is that the interaction of gpIb on resting platelets with P-selectin on activated platelets is involved in growth of thrombi and in promoting platelet aggregation by acting synergistically with subthreshold concentrations of platelet agonists. Leukocytes interact with the surfaces of adherent platelets by attachment, rolling, firm adhesion and migration through the surface. L selectin and Mac-1 have been identified as leukocyte receptors for these events, but the platelet counter-receptors have not yet been identified. Preliminary data from the PI indicates that the gpIb complex is a likely candidate counter-receptor for both rolling and firm adhesion. The experiments proposed in this application will test these hypotheses in model systems and in vivo and will characterize in detail the interactions between gpIb and P-selectin, L-selectin, and Mac-1.